Bone Loss and Immune Reconstitution in HIV/AIDS (BLIR-HIV) (BLIR-HIV)

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With the increasing age of people living with HIV/AIDS, age-induced osteoporosis is likely to be compounded by HIV/AIDS and HAART-associated bone loss. Mechanistically, osteoclasts the cells responsible for bone resorption form under the influence of the key osteoclastogenic cytokine Receptor- Activator of NF-KB (RANKL). The osteoclastogenic and proresorptive activities of RANKL are moderated by its physiological decoy receptor osteoprotegerin (OPG). Imbalance in the ratio of RANKL to OPG alters osteoclastic bone resorption and lead to osteoporosis. Activated T- and B-cells are a major source of RANKL, while normal physiological B-cells are a major source of OPG. T-cells regulate the production of OPG by B-cells. Thus changes in the immune system induced by HIV/AIDS and/or by HAART could affect B-cell and T-cells RANKL and OPG production. Indeed, data from our group shows that in an animal model of HIV/AIDS, the HIV-1 Transgenic rat, the development of osteoporosis is recapitulated as observed in HIV-infected patients, and B-cell OPG and RANKL production are concurrently down regulated and upregulated respectively. Furthermore, preliminary data in HIV-infected subjects suggests dramatic acute upswing in bone resorption following HAART initiation that peaks at 12 weeks and then declines. Based on these findings, the investigators hypothesize HAART associated bone loss is driven by immune reconstitution. Because this effect of HAART is dramatic in magnitude but short in duration, the investigators propose to apply antiresorptive agent (zoledronic acid, reclast®) to specifically spare patients from this dramatic but acute bone damage.

In the primary analysis, changes in serum CTx level, BMD, and cellular OPG/RANKL expression from baseline through week 24 will be quantitated and subsequently compared between treatment arms. In addition, the impact of zoledronic acid administration on these covariates will be assessed at various study time points. The relationship between OPG/RANKL expression, immune activation, serum bone regulating hormonal levels, and bone turnover will be evaluated.

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Ages Eligible for Study:

30 Years to 50 Years (Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

HIV-1 infection, as documented by any licensed serologic test and confirmed by a western blot or by a positive plasma HIV-1 RNA performed by any laboratory that has a CLIA certification.

Meets Grady IDP clinical criteria for antiretroviral therapy initiation, and subject and his/her provider are agreeable to subject initiating therapy with a regimen consisting of ATV/RTV + FTC/TDF as part of his/her routine HIV management.

Ambulatory men and women age ≥ 30 ≤ 50 years.

Ability and willingness of subject or legal guardian/representative to give written informed consent.

ARV drug-naïve (defined as ≤ 10 days of ART at any time prior to entry).

Screening HIV-1 RNA ≥ 1000 copies/mL obtained within 90 days prior to study entry by any FDA-approved test for quantifying HIV-1 RNA at any laboratory that has a CLIA certification.

Absence of history of non-HIV related active immunological or bone disorders such as:

Bone marrow or organ transplantation

Inflammatory bowel disease (ulcerative colitis, Crohn's disease)

Multiple Myeloma

Osteogenesis imperfecta

Osteomalacia

Osteosarcoma

Paget's disease

Postmenopausal osteoporosis

Rheumatoid arthritis

Systemic lupus erythematosus

Thyroid disorders (hyper/hypothyroidism)

Contraception requirements

Female Subjects of Reproductive Potential:

Female subjects of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable method of contraception while participating in the study. Acceptable methods of contraception include:

Currently (within the past 8 weeks) taking any medication with known influence on the immune or skeletal system (e.g. immune modulation therapy, glucocorticoids, steroid hormones, other bisphosphonates).

Osteoporosis defined as T-score <-2.5 at the hip, or spine, or history of osteoporotic fracture.

Known allergy/sensitivity to study drugs or their formulations or mammalian cell derived drug products.

Any condition that, in the opinion of the investigators, would compromise the subject's ability to participate in the study.

Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigators, for at least 7 days prior to study entry.

Requirement for any current medications that are prohibited with any study drugs. Prohibited medications must be discontinued at least 30 days prior to entry.

Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical illness.